DISSOCIATION OF K(ATP) CHANNEL AND SULFONYLUREA RECEPTOR IN THE RAT CLONAL INSULIN-SECRETING CELL-LINE, CRI-D11

It is generally considered that the sulphonylurea receptor is an integ ral part of the ATP-sensitive K+ channel. We have investigated this pr oposal by comparing the binding and functional characteristics of the sulphonylurea receptor and K(ATP) channel by using two rat insulinoma cell lines (CRI-G1 and CRI-D11) of common origin. Insulin release was increased in both cell lines by a variety of metabolizable and non-met abolizable secretagogues but glibenclamide induced an increase in insu lin release in G1 cells only. [H-3]glibenclamide binding studies showe d a substantial reduction in the number of glibenclamide binding sites (B(max)) in the D11 cells compared with G1 cells. Single-channel stud ies of these cell lines show that the K(ATP) channel is generally unch anged in its biophysical properties and in the number of channels obse rved. Slight differences were apparent: the K(ATP) channels in D11 cel ls were much less susceptible to rundown and were slightly less sensit ive to block by ATP. However, one major distinction was the lack or mu ch reduced sensitivity of the K(ATP) channel in D11 cells to tolbutami de and glibenclamide. We conclude that the K(ATP) Channel can exist an d function independently of the sulphonylurea receptor, and therefore it is unlikely that they exist as a single protein assembly.